Rotameric Heterogeneity of Conserved Tryptophan Is Responsible for Reduced Photochemical Quantum Yield in Cyanobacteriochrome Slr1393g3.

The red/green cyanobacteriochrome (CBCR) slr1393g3 exhibits a quantum yield of only 8 % for its forward photoconversion, significantly lower than other species from the same CBCR subfamily. The cause for this reduced photoconversion is not yet clear, although in the related NpR6012g4 dark-state structural heterogeneity of a paramount Trp residue has been proposed to cause the formation of nonproductive subpopulation. However, there is no such information on the equivalent residue in slr1393g3, W496.

Oxygen accumulation and associated dangers in rescue helicopters.

Background: At the time of the COVID-19 pandemic, devastating incidents increased due to frequent oxygen administration to patients. The dangers associated with the use of oxygen, especially through local enrichments and formation of "oxygen clouds", have been well understood for years. Nevertheless, dramatic incidents continue to occur, since fire hazard increases exponentially with oxygen concentrations above 23%.

Red Shift in the Absorption Spectrum of Phototropin LOV1 upon the Formation of a Semiquinone Radical: Reconstructing the Orbital Architecture.

Flavin mononucleotide (FMN) is a ubiquitous blue-light pigment due to its ability to drive one- and two-electron transfer reactions. In both light-oxygen-voltage (LOV) domains of phototropin from the green algae , FMN is noncovalently bound. In the LOV1 cysteine-to-serine mutant (C57S), light-induced electron transfer from a nearby tryptophan occurs, and a transient spin-correlated radical pair (SCRP) is formed.

Conserved tyrosine in phytochromes controls the photodynamics through steric demand and hydrogen bonding capabilities.

Using ultrafast spectroscopy and site-specific mutagenesis, we demonstrate the central role of a conserved tyrosine within the chromophore binding pocket in the forward (P → P) photoconversion of phytochromes. Taking GAF1 of the knotless phytochrome All2699g1 from Nostoc as representative member of phytochromes, it was found that the mutations have no influence on the early (<30 ps) dynamics associated with conformational changes of the chromophore in the excited state. Conversely, they drastically impact the extended protein-controlled excited state decay (>100 ps).

Photocycle of a cyanobacteriochrome: a charge defect on ring impairs conjugation in chromophore.

A large number of novel phytochromes named cyanobacteriochromes (CBCRs) have been recently identified. CBCRs appear to be attractive for further in-depth studies as paradigms for phytochromes because of their related photochemistry, but simpler domain architecture. Elucidating the mechanisms of spectral tuning for the bilin chromophore down to the molecular/atomic level is a prerequisite to design fine-tuned photoswitches for optogenetics.

Stabilization of a flavoprotein for solid-state photo-CIDNP MAS NMR at room temperature by embedding in a glassy sugar matrix.

Hyperpolarization via the solid-state photochemically induced dynamic nuclear polarization (photo-CIDNP) effect can be detected in frozen solutions of electron transfer proteins generating a radical-pair upon illumination. The effect has been observed in various natural photosynthetic reaction centers and in light-oxygen-voltage (LOV) sensing domains incorporating a flavin mononucleotide (FMN) as chromophore. In LOV domains, where a highly conserved cysteine is mutated to a flavin to interrupt its natural photochemistry, a radical-pair is generated by electron transfer from a nearby tryptophan to the photoexcited triplet state of FMN.

Elevated methemoglobin levels in patients treated with high-dose hydroxocobalamin.

Objective: The aim of this study was to assess the impact of hydroxocobalamin (OHCbl) infusion on arterial blood gas and oximetry values in patients with vasoplegic syndrome.

Methods: Blood samples collected from 95 patients receiving OHCbl infusion were assayed using the ABL90 FLEX Plus blood gas analyzer for the concentration of methemoglobin (MetHb), total hemoglobin (tHb), carboxyhemoglobin (COHb), arterial oxygen saturation (SaO2), arterial oxygen partial pressure (PaO2), and arterial carbon dioxide partial pressure (PaCO2). Interference of OHCbl on these variables was evaluated using the measured difference between the preinfusion and postinfusion samples.

Influence of the PHY domain on the ms-photoconversion dynamics of a knotless phytochrome.

The ability of some knotless phytochromes to photoconvert without the PHY domain allows evaluation of the distinct effect of the PHY domain on their photodynamics. Here, we compare the ms dynamics of the single GAF domain (g1) and the GAF-PHY (g1g2) construct of the knotless phytochrome All2699 from cyanobacterium Nostoc punctiforme. While the spectral signatures and occurrence of the intermediates are mostly unchanged by the domain composition, the presence of the PHY domain slows down the early forward and reverse dynamics involving chromophore and protein binding pocket relaxation.

Light- and pH-dependent structural changes in cyanobacteriochrome AnPixJg2.

Cyanobacteriochromes (CBCRs) are phytochrome-related photosensory proteins that play an essential role in regulating phototaxis, chromatic acclimation, and cell aggregation in cyanobacteria. Here, we apply solid-state NMR spectroscopy to the red/green GAF2 domain of the CBCR AnPixJ assembled in vitro with a uniformly C- and N-labeled bilin chromophore, tracking changes in electronic structure, geometry, and structural heterogeneity of the chromophore as well as intimate contacts between the chromophore and protein residues in the photocycle. Our data confirm that the bilin ring D is strongly twisted with respect to the B-C plane in both dark and photoproduct states.

The Impact of Anticoagulation on COVID-19 (SARS CoV-2) Patient Outcomes: A Systematic Review.

Background: Emerging data suggest that coagulopathy, cytokine storm, and acute respiratory distress syndrome are associated with the 2019 coronavirus disease (COVID-19). The prevalence of hypercoagulable state in these patients is unknown, but appears to be higher compared to those with other critically ill patients. Elevated D-dimer, large blood vessels clots, deep vein thrombosis, pulmonary embolism and disseminated intravascular coagulation have been reported in patients diagnosed with COVID-19 either on admission or during hospitalization and may be predictors of poor outcomes.

Hydrogen Bond between a Tyrosine Residue and the -Ring Propionate Has a Direct Influence on Conformation and Absorption of the Bilin Cofactor in Red/Green Cyanobacteriochromes.

Cyanobacteriochromes (CBCRs) are photoreceptors of the phytochrome superfamily showing remarkable variability in the wavelengths of the first electronic transition-sometimes denoted as Q band-compared to canonical phytochromes. Both classes carry the same cofactor, a bilin, but the molecular basis for the wide variation of their absorption properties is still a matter of debate. The interaction between the cofactor and the surrounding protein moiety has been proposed as a possible tuning factor.

Volumetric measurements of paranasal sinuses and examination of sinonasal communication in healthy Shetland ponies: anatomical and morphometric characteristics using computed tomography.

Background: Despite clinical importance and frequent occurrence of sinus disease, little is known about the size of paranasal sinuses and their communication in ponies and small horses. To examine the shape and volume of the paranasal sinuses and evaluate the sinonasal communication, three-dimensional (3D) reconstructions of computed tomography (CT) datasets of 12 healthy adult Shetland ponies were performed and analysed. Linear measurements of head length and width were taken.

Integral Use of Thromboelastography With Platelet Mapping to Guide Appropriate Treatment, Avoid Complications, and Improve Survival of Patients With Coronavirus Disease 2019-Related Coagulopathy.

Objectives: Coagulopathy of coronavirus disease 2019 is largely described as hypercoagulability, yet both thrombotic and hemorrhagic complications occur. Although therapeutic and prophylactic anticoagulant interventions have been recommended, empiric use of antifactor medications (heparin/enoxaparin) may result in hemorrhagic complications, including death. Furthermore, traditional (antifactor) anticoagulation does not address the impact of overactive platelets in coronavirus disease 2019.

An anatomical study of the dorsal and ventral nasal conchal bullae and middle nasal conchae in normal Shetland ponies: Computed tomographic anatomical and morphometric findings.

Equine paranasal sinuses are susceptible to inflammation. Insufficient drainage through the nasal passages and meatus may lead to the accumulation of inspissated purulent discharge. Particularly in ponies, these anatomical structures are suspected to be relatively small.

Scoping review of biological treatment of deficiency of interleukin-36 receptor antagonist (DITRA) in children and adolescents.

Background: Deficiency of interleukin-36 receptor antagonist (DITRA) is a life threatening monogenic autoinflammatory disease caused by loss of function mutations in the IL36RN gene. Affected patients develop recurrent episodes of generalized pustular psoriasis (GPP) with systemic inflammation and fever. We here review and analyze the literature on pediatric DITRA patients who have been treated by biologicals targeting inflammatory cytokines.

Carfentanil and Current Opioid Trends in Summit County, Ohio.

Introduction: The Summit County Medical Examiner's Office (SCMEO) observed 52 unexplained deaths during the month of July 2016 in which drug overdose was suspected. A fentanyl screening immunoassay performed on autopsy specimens was positive, but gas chromatograph/mass spectrometry (GC/MS) failed to confirm its presence. Carfentanil, a large wildlife tranquilizer, was later identified through reference lab testing as the cause of the sudden increase in overdoses.

The Doktabörse - an innovative online platform for research projects at the medical faculty of the LMU Munich.

One of the most important extracurricular aspects of medical studies in Germany is a research thesis completed by most students. This research project often times conveys relevant competencies for the physician's role as scientist. Nevertheless, the choice of the right project remains a challenge.

Exome sequencing identifies a novel EP300 frame shift mutation in a patient with features that overlap Cornelia de Lange syndrome.

Rubinstein-Taybi syndrome (RTS) and Cornelia de Lange syndrome (CdLS) are genetically heterogeneous multiple anomalies syndromes, each having a distinctive facial gestalt. Two genes (CREBBP and EP300) are known to cause RTS, and five (NIPBL, SMC1A, SMC3, RAD21, and HDAC8) have been associated with CdLS. A diagnosis of RTS or CdLS is molecularly confirmed in only 65% of clinically identified cases, suggesting that additional causative genes exist for both conditions.

A clinical pharmacist's role in screening for metabolic syndrome in a rural pediatric ambulatory clinic.

Purpose: The prevalence of metabolic syndrome in the pediatric population is increasing. Barriers, including the lack of consensus of a definition for metabolic syndrome and time constraints for the pediatrician, may limit the identification and diagnosis of metabolic syndrome in children. The objective of this pilot study was to evaluate the role of a clinical pharmacist (CP) in screening children and adolescents for metabolic syndrome.

Erdheim-chester disease associated with marginal zone lymphoma and monoclonal proteinemia.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. We report a fatal case of ECD with extensive cardiac involvement associated with a marginal zone lymphoma and monoclonal proteinemia in a young man. This is the first reported association of ECD with a monoclonal gammopathy or a lymphoma.

Deaths associated with liposuction: case reports and review of the literature.

Tumescent liposuction is a common cosmetic procedure that is performed as an outpatient service in physician's offices and is largely believed to be safe. The protuberant areas of the body containing the undesirable fat deposits are injected with normal saline containing lidocaine and epinephrine for pain control and hemostasis, and the waterlogged cells are suctioned out via cannula through a small incision. We recently encountered three cases in which deaths were attributed to this procedure.